The goal of this proposal is to elucidate the physiological mechanisms by which the primate corpus luteum is regulated and maintained during menstrual cycle. To accomplish this, we will use female rhesus monkeys whose gonadotropin secretion is controlled by pulsatile administration of exogenous gonadotropin releasing hormone (GnRH). With this model system, it will be possible to "functionally hypophysectomize" rhesus monkeys at any stage of the luteal phase of the menstrual cycle simply by terminating the GnRH infusion. Gonadotropin secretion may be restored any time thereafter simply by resuming the GnRH infusion. Furthermore, the temporal pattern of serum gonadotropin levels to which the corpus luteum is exposed may be controlled precisely by varying the frequency of exogenous GnRH pulses. We will use this model system to define the dependency of corpus luteum on pituitary gonadotropins during the early, mid, and late luteal phase of the menstrual cycle; to identify the nature by which the corpus luteum perceives and responds to pituitary gonadotropins and to eulucidate the site of action of estradiol in promoting luteal regression. In addition to providing definitive information regarding the physiological regulation of the primate corpus luteum in vivo, the data obtained from these experiments may further our understanding of pathophysiological disturbances of the human menstrual cycle such as the shor luteal phase and the inadequate luteal phase. Lastly, it is becoming increasingly apparent that pulsatile GnRH treatment will be used extensively in the treatment of certain types of amenorrhea in humans. The studies described in this proposal will provide important information regarding the maintenance of the corpus luteum in GnRH driven menstrual cycles, and in so doing, may directly guide clinical endocrinologists in the effective treatment of infertility in humans.